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PubMed2002

Cytokeratins 7 and 20, Dpc4, and MUC5AC in the distinction of metastatic mucinous carcinomas in the ovary from primary ovarian mucinous tumors: Dpc4 assists in identifying metastatic pancreatic carcinomas.

The distinction of metastatic mucinous carcinomas in the ovary from primary ovarian mucinous tumors (atypical proliferative/borderline and carcinoma) can be difficult because of similarities in morphology. We evaluated the immunohistochemical expression of cytokeratins 7 and 20 (CK 7, CK 20), Dpc4 (nuclear transcription factor inactivated in 55% of pancreatic carcinomas), and MUC5AC (a gastric mucin gene) in 57 primary ovarian mucinous tumors (41 atypical proliferative tumors and 16 carcinomas) and 46 metastatic mucinous carcinomas in the ovary. Primary ovarian mucinous tumors were virtually always diffusely positive for CK 7 (98%), Dpc4 (100%), and MUC5AC (98%) and often focally to diffusely positive for CK 20 (68%). Colorectal mucinous carcinomas were diffusely positive for CK 20 (100%) and Dpc4 (89%) and were distinguished from primary ovarian mucinous tumors by their frequent lack of expression of CK 7 and MUC5AC (67% were negative for each marker). Appendiceal carcinomas were diffusely positive for CK 20 (100%) and often negative for CK 7 (71%) but were often positive for MUC5AC (86%) and Dpc4 (100%). When primary ovarian and metastatic colorectal or appendiceal carcinomas shared expression of both CK 7 and CK 20, they could usually be distinguished by the pattern of positivity (diffuse CK 7 and patchy CK 20 in ovarian tumors and patchy CK 7 and diffuse CK 20 in colorectal and appendiceal tumors). Pancreatic carcinomas shared the same pattern of diffuse positivity for CK 7 (100%) and MUC5AC (92%) and focal to diffuse positivity for CK 20 (71%) as primary ovarian mucinous tumors but were negative for Dpc4 in 46%. Loss of Dpc4 expression is useful for distinguishing metastatic pancreatic carcinomas in the ovary from both primary ovarian mucinous tumors and metastatic mucinous carcinomas derived from other sites.

Adenocarcinoma, Mucinous↗
PubMed1996

Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites.

To test the possibility of immunohistochemical differentiation of cytostatically treatable metastatic breast carcinomas from other metastatic adenocarcinomas of unknown primary site, we studied a total of 328 metastatic adenocarcinomas including 35 bronchogenic, 26 pancreatic, 25 colonic, 39 gastric, 45 renal, 29 ovarian and 129 breast carcinomas with a panel of 13 commercially available monoclonal antibodies. The expression of gross cystic disease fluid protein 15 and/or oestrogen or progesterone receptors had a sensitivity of 0.83, a specificity of 0.93 and a predictive accuracy of 0.92 for carcinomas of the breast against all other carcinomas. Excluding ovarian carcinomas, this combination had a sensitivity, specificity and predictive accuracy for mammary carcinomas of 0.83, 0.98 and 0.98, respectively. Carcinoembryonic antigen and/or cytokeratin 20 identified bronchogenic, gastric, pancreatic and colorectal carcinomas versus breast carcinomas lacking gross cystic disease fluid protein 15 and oestrogen or progesterone receptors with a sensitivity, specificity and predictive accuracy of 0.82, 0.99 and 0.95, respectively. Vimentin differentiates renal cell carcinomas from gross cystic disease fluid protein 15 and oestrogene or progesterone receptor negative breast carcinomas with a sensitivity, specificity and predictive accuracy of 0.93, 0.82 and 0.84. Thus, it should be possible to differentiate most metastatic mammary carcinomas from metastatic adenocarcinomas of other common primary sites, even if the former lack expression of gross cystic disease fluid protein 15 and oestrogen or progesterone receptors.

Adenocarcinoma↗
PubMed1993

Transfection of metastatic capability with total genomic DNA from human and mouse metastatic tumour cell lines.

From a large series of experiments involving transfer of high molecular weight total genomic DNA from highly metastatic human and mouse tumour cell lines to other mouse tumour cell lines we have derived a few cell lines with greatly augmented metastatic properties. In one of these experiments the transfected cell line (designated AH8 Test) not only colonised the lungs but also formed secondary tumour colonies in several extrapulmonary sites including the skin, skeletal muscles, bone, liver diaphragm, spleen and heart. There were no qualitative and quantitative effects of this magnitude when we used DNA from several non-metastatic or non-tumourigenic sources. Secondary transfection of metastatic capability with DNA obtained from a metastasis formed by one of the primary transfectant lines (AH8 Test) has also been accomplished. Concomitant transfer of human DNA through both transfection cycles in this experiment was confirmed by a variety of methods including Southern blot analysis, in situ hybridisation and polymerase chain reaction (PCR) amplification of DNA using primers recognising human-specific Alu repeat sequences. The findings offer opportunities for the isolation of sequences programming metastatic behaviour and we have cloned and sequenced a fragment of human DNA, which has not been previously characterised, from the transfected cells.

Animals↗
PubMed1983

Comparison of iodinated antigens of metastatic and non-metastatic mammary adenocarcinoma cells.

The surface and detergent-soluble proteins of metastatic (TMT-081) and nonmetastatic (MT-100) mammary adenocarcinoma cells were labeled using [125I]-lactoperoxidase. The iodinated proteins were analyzed by SDS-gel electrophoresis and autoradiography. The results revealed seven iodinated surface polypeptides in metastatic cells with molecular weights of 150,000, 130,000, 110,000, 78,000, 67,000, 40,000 and 22,000. The nonmetastatic cell surface revealed eight iodinated polypeptides with molecular weights of 175,000, 150,000, 130,000, 120,000, 110,000, 67,000, 40,000, and 24,000. The small molecular weight polypeptides, 22,000-24,000, of both metastatic and nonmetastatic cells were the most intensely labeled and appeared as a major surface component. Iodination of the detergent-soluble proteins in tumor extracts results in the labeling of five polypeptides (175,000, 67,000, 44,000, 29,000, 22,000 MW) of metastatic tumor and six polypeptides (175,000, 78,000, 67,000, 40,000, 35,000, 22,000 MW) of nonmetastatic tumor. Immunoprecipitation analyses indicate that the iodinated tumor polypeptides are antigenic to a xenogenic host. The 175,000 MW surface polypeptide of nonmetastatic and the 40,000 MW polypeptide of metastatic cells were not detected in the immunoprecipitates. The results of immunoprecipitation suggest that the small molecular weight (22,000-24,000) polypeptides are the predominant antigens of both tumor cells.

Adenocarcinoma↗
PubMed2003

Differential effects of retinoic acid on the growth of isogenic metastatic and non-metastatic breast cancer cell lines and their association with distinct expression of retinoic acid receptor beta isoforms 2 and 4.

The human retinoic acid receptor beta (RARbeta) has three isoforms (beta1, beta2, and beta4), which play important, distinct roles in mediating the effects of retinoic acid on cell growth and apoptosis. Whereas RARbeta2 is a potent inhibitor of breast cancer cell proliferation, RARbeta4 can act as a dominant-negative repressor of RARbeta2-mediated growth suppression. In this study we investigated the effects of all-trans-retinoic acid (ATRA) on two clones derived from the breast cancer cell line MDA-MB-435: a non-metastatic clone (NM-2C5) and a metastatic clone (M-4A4). ATRA treatment of the NM-2C5 cells resulted in growth inhibition and apoptosis, whereas the M-4A4 cells were resistant to ATRA. Analyses of the expression of RARbeta isoforms revealed that the sensitive NM-2C5 clone expressed only RARbeta2, whereas the resistant M-4A4 cells expressed both RARbeta2 and RARbeta4 mRNA and protein. ATRA treatment increased RARbeta2 mRNA level in NM-2C5 cells, whereas the same treatment of the M-4A4 cells resulted in an increase in RARbeta4 and a decrease in RARbeta2 mRNA. ATRA treatment of NM-2C5 cells increased the protein levels of the histone acetyl transferases p300 and CBP, suppressed the level of histone deacetylase and increased the level of acetylated histone H4. ATRA also decreased Bcl-2 and increased Bax and decreased VEGF. In contrast, the same treatment of the M-4A4 cells resulted in opposite effects. These results suggest that the effects of ATRA on the growth of the metastatic and non-metastatic breast cancer cell lines depend on the expression of RARbeta isoforms and that the expression of RARbeta4 may contribute to metastatic properties.

Adenocarcinoma↗
PubMed1988

The immunobiology of metastatic processes: analysis of NK sensitivity and the metastatic potential of H-2 gene transfected fibrosarcoma cells.

The transformation of a potentially neoplastic cell into an autonomous highly malignant and metastatic tumor cell involves a multifactorial cascade of events. This will eventually lead not only to the emergence of a tumor cell with an unlimited potential of replication, but more important will contribute to its ability to ignore and evade homeostatic immune and nonimmune regulatory mechanisms. Specifically, those mechanisms which may restrict and direct its growth, dissemination, patterns of differentiation and interaction with the cellular and humoral factors comprising its environment. In the present studies we have investigated the contribution of three major factors which may be the cause or result of alterations at the level of the cell membrane: MHC encoded antigen expression, susceptibility to the cytolytic activity of NK cells and enhanced expression of the c-K-ras proto-oncogene, as to their development of the metastatic capacity of a malignant cell. To address these questions we used metastatic (IE7) and nonmetastatic (IC9) variants of the murine 3-methylcholanthrene-induced T-10 fibrosarcoma. Using this system, the following major conceptually important observations were made: (A) The restoration by transfection of the expression of membrane associated H-2K encoded glycoproteins abrogates the metastatic capacity of the highly metastatic tumor cell clone, IE7, irrespective of the degree of susceptibility to NK or c-K-ras oncogene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Osteosarcoma of the extremities metastatic at presentation. Results obtained with primary chemotherapy followed by simultaneous resection of the primary and metastatic lesion].

From September 1986 to September 1990 35 patients affected by osteosarcoma of the extremities with synchronous metastasis were treated with two cycles of high-dose methotrexate IV, cisplatin IA and adriamycin IV followed, in 22, by simultaneous resection of the primary and metastatic tumor. Six patients progressed and were not operated on, 7 patients with complete response of pulmonary nodules underwent surgical resection of the primary lesion. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumour was "good" (90% or more tumour necrosis) in 8 patients (27%) and "poor" (less than 90% of tumour necrosis) in 21 (73%) while in the 75 metastatic nodules the resulting necrosis was good in 18 (24%) and poor in 57 (74%). A good correlation between the histological response in the primary and metastatic tumour was observed. At an average follow-up of 30 months (R 12-60), 13 patients are alive, 10 disease-free, and 3 with uncontrolled disease. This data suggest that prognosis of osteosarcoma of the extremities with synchronous metastases remains poor even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non metastatic osteosarcoma: to introduce new drugs postoperatively in patients poor responder can allows a better treatment of microscopic disease and can improve the prognosis for these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Generation of invasive and metastatic variants of a non-metastatic T-cell lymphoma by in vivo fusion with normal host cells.

Intravenous inoculation of the AKR mouse-strain-derived BW lymphoma into CBA recipients resulted in a case of liver metastasis; cells derived from this metastatic nodule were termed BW-Li cells. BW-Li cells, upon reinoculation, generated metastases in the spleen, liver, kidney and ovaries in 100% of CBA recipients. Furthermore, BW-Li cells, in contrast to BW cells, were found to infiltrate in vitro monolayers of hepatocytes, thus confirming their inherent invasive potential. Analysis of the alloantigenic phenotype of BW-Li cells revealed that such cells were Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2- and H-2Dk+, as compared to BW cells which exhibited the membrane phenotype Thy 1.1+, Thy 1.2-, Lyt 1.2-, Lyt 1.1-, Lyt 2-, H-2Dk-. BW-Li cells also differed functionally from BW cells since these cells secreted IL-2 upon stimulation with Concanavalin A. BW tumor transplantation experiments were repeated in a semi-allogeneic F1 strain combination, i.e. (AKR X CBA)F1, and again a case of massive liver metastasis was observed. Cells derived from these liver metastases (termed BW-O-Li) manifested an invasive and metastatic potential similar to that of BW-Li cells. Furthermore, BW-O-Li cells secreted IL-2 upon stimulation with Con A and manifested the following alloantigenic phenotype: Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1-, Lyt 2-, H-2Dk+ and H-2Kk+. These results indicate that BW-Li and BW-O-Li cells are functional T-cell hybrids which express T-cell markers derived from BW cells and Thy 1.2+ CBA host cells. The acquisition of host-derived T-cell properties may have led to the expression of metastatic and invasive capabilities. From these results we conclude that the acquisition of metastatic properties following somatic cell fusion with normal lymphoreticular cells may represent a mechanism for tumor progression in vivo.

Animals↗
PubMed2004

Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions.

CD1 molecules are expressed by antigen-presenting cells such as dendritic cells and mediate primary immune responses to lipids and glycolipids which have been shown to be expressed by various tumors. Glycolipids are expressed by melanoma cells but, despite their immunogenicity, no efficient spontaneous immune responses are elicited. As IL-10 has previously been shown to down-regulate CD1a on dendritic cells and is known to be expressed by various melanoma cell lines, we investigated if melanoma-derived IL-10 could down-regulate CD1 molecule expression on dendritic cells as a possible way to circumvent immune recognition. We found that CD1a, CD1b, CD1c, and CD1d were significantly down-regulated on dendritic cells in metastatic (n = 10) but not in primary melanoma lesions (n = 10). We further detected significantly higher IL-10 protein levels in metastatic than in primary melanomas. Moreover, supernatants from metastatic melanomas were significantly more effective in down-regulating CD1 molecules on dendritic cells than supernatants from primary melanoma cultures. This effect was blocked using a neutralizing IL-10 antibody in a dose dependent manner. Our findings suggest that metastatic but not primary melanomas can down-regulate CD1 molecules on infiltrating dendritic cells by secreting IL-10 which may represent a novel way to escape the immune response directed against the tumor.

Antigens, CD1↗
PubMed1992

Metastatic bronchioloalveolar carcinoma and metastatic adenocarcinoma of the lung: comparison of clinical manifestations, chemotherapeutic responses, and prognosis.

Between 1975 and 1985, 25 patients with metastatic bronchioloalveolar carcinoma and 223 patients with metastatic adenocarcinoma of the lung received experimental cisplatin-based chemotherapy at the Mayo Clinic. The chemotherapeutic response rates were 32% and 33%, respectively. The median times to progression of disease were identical (3 months in both groups). The median survival times were 4 months and 6 months, respectively. Metastatic bronchioloalveolar carcinoma is an aggressive disease that is associated with a poor prognosis, similar to metastatic adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1999

Molecular cloning of a novel human PAPS synthetase which is differentially expressed in metastatic and non-metastatic colon carcinoma cells.

Subtractive hybridisation was used to select for genes which are differentially expressed between a highly metastatic human colon carcinoma cell line, KM12SM, and the isogenetic non-metastatic cell line, KM12C. This led to the isolation of cDNA clones for a novel human adenosine 5'-phosphosulphate kinase/ATP sulphurylase (PAPS synthetase). Northern hybridisation revealed a single 4.2 kb mRNA species which showed an approximately 20-fold higher level of expression in the non-metastatic cell line than in the metastatic cell line. The overlapping cDNA clones together covered 3,774 bp including the entire coding region of 1,842 bp encoding a protein of 614 amino acids (calculated molecular mass of 69,496 Da). The protein contains consensus sequences for APS kinase and ATP sulphurylase, in its amino- and carboxy-terminal regions, respectively, as well as other sequences that are highly conserved amongst ATP sulphurylases and APS kinases. Interestingly, consensus sequences for GTPase activity were also identified, indicating that enzyme activity may be regulated by an intrinsic GTPase mechanism. Overall the new protein is 78% homologous with a previously described human PAPS synthetase (PAPSS1) indicating that we have identified the second member of a gene family which we have provisionally named PAPSS2. The gene locus for PAPSS2 was identified on chromosome 10 at 10q23.1-q23.2. This locus has synteny with the mouse brachymorphic gene recently identified as a PAPS synthetase (SK2). PAPSS2 appears to be the human homologue of this gene and thus PAPSS2 is likely to be important in human skeletogenesis.

Amino Acid Sequence↗
PubMed1998

Angiogenic capacity and lung-colonizing potential in vivo is increased in weakly metastatic B16F1 cells and decreased in highly metastatic BL6 cells by phorbol esters.

The development of tumor metastasis is a multistep process. Key aspects of this process are the interaction of tumor cells with the extracellular matrix, digestion of, and motility through the basement membrane and the induction of angiogenesis. In this study, we analysed the effects of a low dose of TPA (12-tetradecanoylphorbol-13-acetate; 0.1 microM on angiogenesis, proteolytic activity and lung colonizing potential of both weakly metastatic B16F1 cells and highly metastatic BL6 murine melanoma cells. Our results demonstrated opposite effects of TPA in the two cell lines. TPA-treated B16F1 cells showed enhanced release of basic FGF (bFGF) and vascular endothelial growth factor (VEGF) and increased angiogenic capacity and lung colony formation in vivo. In contrast, TPA-treated BL6 cells demonstrated a dramatic reduction of angiogenic and gelatinolytic activity and metastatic capacity. However, both cell lines showed an induction of VEGF as well as bFGF expression by TPA treatment suggesting that in BL6 cells antagonistic factors, inhibiting the angiogenic and metastatic capacity, are induced by this treatment.

Animals↗
PubMed1999

Metastatic and non-metastatic colorectal cancer (CRC) cells induce host metalloproteinase production in vivo.

Numerous studies have demonstrated the persistent localization of matrix metalloproteinase (MMP) expression to the interface between invading human colorectal cancer (CRC) cells and surrounding stroma supporting a role for MMPs in CRC invasion and metastasis. The present study sought to determine whether CRC cells of varying metastatic potential would have differential effects on host MMP release. Subcutaneous CRC tumors were generated in BALB/c nude mice using three CRC cell lines: SW480, SW620, and the highly metastatic SW620S5 clone. Representative samples from the subcutaneous CRC were then orthotopically implanted on the cecum of recipient nude mice. Subcutaneous and cecal tumors were analyzed for MMP expression via zymography, western blot, and RT-PCR. In vitro, none of the three cell lines expressed MMP-2 nor MMP-9. In contradistinction, the subcutaneous tumors expressed limited amounts of MMP-2 and MMP-9 while the cecal tumors expressed significant amounts of MMP-2 and MMP-9 as well as other smaller members of the MMP family. MMP-9 mRNA and protein was confirmed as host in origin by RT-PCR with mouse specific primers and a mouse MMP-9 molecular weight of 105 kDa as determined by zymography and western blot analysis. In situ hybridization also localized the mRNA for MMP-9 to the host stromal cells. In conclusion, CRC cells appear incapable of producing MMP-2 and MMP-9 in vitro but are capable of up-regulating host MMP production in vivo. Enhanced host MMP-9 production in metastatic CRC cell-derived subcutaneous and cecal tumors suggests that metastatic colon cells may acquire the expression of important MMP regulating factor(s) in vivo.

Animals↗
PubMed1997

Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells.

S100A4 (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin /FSP1/CAPL), a member of S100-related calcium-binding proteins, has been implicated to play a role in metastasis. In the present study, we examined the effect of antisense S100A4 RNA on metastatic potential of Lewis lung carcinoma (LLC) cells. High-metastatic All cells were transfected with the expression vector containing S100A4 cDNA in an inverted (antisense) orientation under the transcriptional control of the mouse metallothionein promoter. Treatment of a stably transfected clone (AS10 cells) with Zn2+ resulted in the suppression of the experimental metastatic ability, which was accompanied with the expression of antisense S100A4 RNA and the suppression of the S100A4 expression at both the mRNA and the protein levels. To further confirm the effect of antisense S100A4 RNA, we established several clones after retroviral transduction with an antisense S100A4 construct. Notably, reduced metastatic potential was also evident in these clones. In the antisense S100A4 RNA-expressing cells, cell motility and in vitro invasiveness were found to be suppressed.

Animals↗
PubMed1996

Independence of metastatic ability and extravasation: metastatic ras-transformed and control fibroblasts extravasate equally well.

Escape of cancer cells from the circulation (extravasation) is thought to be a major rate-limiting step in metastasis, with few cells being able to extravasate. Furthermore, highly metastatic cells are believed to extravasate more readily than poorly metastatic cells. We assessed in vivo the extravasation ability of highly metastatic ras-transformed NIH 3T3 cells (PAP2) versus control nontumorigenic nontransformed NIH 3T3 cells and primary mouse embryo fibroblasts. Fluorescently labeled cells were injected intravenously into chicken embryo chorioallantoic membrane and analyzed by intravital videomicroscopy. The chorioallantoic membrane is an appropriate model for studying extravasation, since, at the embryonic stage used, the microvasculature exhibits a continuous basement membrane and adult permeability properties. The kinetics of extravasation were assessed by determining whether individual cells (n = 1481) were intravascular, extravascular, or in the process of extravasation, at 3, 6, and 24 h after injection. Contrary to expectations, our results showed that all three cell types extravasated with the same kinetics. By 24 h after injection > 89% of observed cells had completed extravasation from the capillary plexus. After extravasation, individual fibroblasts of all cell types demonstrated preferential migration within the mesenchymal layer toward arterioles, not to venules or lymphatics. Thus in this model and for these cells, extravasation is independent of metastatic ability. This suggests that the ability to extravasate in vivo is not necessarily predictive of subsequent metastasis formation, and that postextravasation events may be key determinants in metastasis.

3T3 Cells↗
PubMed2001

Metastatic lesions in the joint associated with acute inflammatory arthritis after dendritic cell immunotherapy for metastatic melanoma.

A 47 year old man undergoing immunotherapy for metastatic melanoma with autologous dendritic cells pulsed with autologous tumour peptide and hepatitis B surface antigen developed acute left ankle arthritis. Gout and acute infection were excluded, and an autoimmune aetiology or occult metastasis were considered. The arthritis initially subsided with indomethacin, but the symptoms recurred 2 months later, and magnetic resonance imaging demonstrated metastatic melanoma of the left talus. Immunohistochemical staining of a cerebral metastatic deposit biopsied 1 week after the onset of arthritis demonstrated T-cell and macrophage infiltration of the tumour. In addition, the patient developed melanoma-specific delayed type hypersensitivity and cytotoxic T-cell responses after vaccination. Thus, the monoarthritis represented an 'appropriate' inflammatory response directed against metastatic melanoma.

Arthritis↗
PubMed2001

Expression of fas ligand in metastatic prostatic carcinoma: suggestive of possible clonal expansion of subpopulation with metastatic potential.

Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases. Analysis of the FasL gene and its mRNA by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively, suggested that the expression of immunohistochemically detectable FasL in metastatic tumor cells was not due to mutation in the FasL gene with resulting overexpression. Further, FasL expression was detectable in the acinar epithelial cells of prostates with morphologic atrophic changes, suggesting that FasL also plays a role in the physiologic apoptosis process of noncancerous prostate. The current data suggest that a subpopulation of prostate carcinoma cells clonally expresses FasL, and this subpopulation may have metastatic potential. Evaluation of FasL expression in the primary tumor thus may provide a useful parameter for predicting metastatic potential of the tumor.

Bone Marrow↗
PubMed1990

Discrepancy between transcriptional products and cell surface expression of MHC class I antigens in metastatic and non-metastatic Lewis lung tumor cells.

Major histocompatibility complex class I transcriptional products and cell surface expression of their corresponding proteins were measured in tumorigenic Lewis lung carcinoma cells with either high metastatic activity (G4 cells) or with no metastatic activity (G2 cells). The transcriptional products were measured by hybridization to gene-specific oligonucleotide probes for H-2Kb and H-2Db respectively. The cell surface density of the corresponding H-2 glycoproteins was determined by FACS cell sorter analysis and by radioimmunoassay using anti-H-2Kb and anti-H-2Db specific monoclonal antibodies. The analyses revealed that the cell surface density of both Kb and Db was reduced 4-9 fold in G4 cells compared to G2 cells. However, this reduction of G4 cell surface expression of MHC class I molecules was not reflected at the mRNA level since both subclones had similar low levels of detectable Kb and Db specific mRNA. beta 2-microglobulin was analysed at the mRNA and protein level and found not to be the rate-limiting factor in the MHC class I expression of the metastatic G4 cells. Thus, the cell surface expression of H-2Kb and H-2Db by the two Lewis lung carcinoma subclones did not correlate with the amount of specific mRNA. Other regulatory mechanisms of gene expression acting at the levels between transcription and the appearance of the gene product at the cell surface must therefore account for the observed difference in the cell surface expression of MHC class I molecules of the two Lewis lung carcinoma cells. The potential importance of MHC class I expression in the metastatic capacity of the tumor cells is discussed.

Animals↗